Megaloblastic and transitional megaloblastic anemia associated with chronic liver disease: A study of nine cases

Abstract

P ATIENTS with liver disease are often anemic [7-51. In some, particularly after acute blood loss, the anemia is normochromic and normocytic in type [6] ; in others, complicated by iron deficiency, hypochromic microcytic anemia may develop [7]. In most cases, however, the anemia is macrocytic [2,8-701. Early workers considered that this macrocytosis was identical with Addisonian pernicious anemia [ 7 7,721 and the result of failure of storage or activation of “hemopoietic principle” in the damaged liver [ 73,741. Subsequently, differences between the macrocytic anemia usually seen in liver disease and pernicious anemia were demonstrated: the bone marrow is generally normoblastic or macronormoblastic in liver disease and invariably megaloblastic in untreated pernicious anemia ; free gastric hydrochloric acid can usually be demonstrated in cirrhosis [Z], whereas achlorhydria is the rule in pernicious anemia [ 741; in cirrhosis the serum level of vitamin Brz is normal or high and the absorption of radioactive vitamin Brz is normal [78], whereas in pernicious anemia the serum level of vitamin Bi2 is reduced and the absorption of labeled vitamin Biz is impaired ; and finally, there is usually little or no hemopoietic response to the administration of vitamin Brz in patients with cirrhosis, in contrast to its efficacy in pernicious anemia [ 74. Megaloblastic hemopoiesis has not been reported often in patients with chronic liver disease. This association is recorded in only thirtysix instances in the literature [72,79-261. Some of these cases undoubtedly represented the coincidental association of classic Addisonian pernicious anemia in patients with chronic liver disease; others, the development of a nutritio.nal deficiency of folic acid or vitamin Brz. However in many instances the pathogenesis of the anemia was obscure and a variety of metabolic faults due to the liver disease were postulated. Gastric acidity and vitamin Brz absorption were tested in some [23] and the serum level of vitamin Brg was estimated in others [24]. The folic acid status in some cases has been assessed by estimations of the urinary levels of “folic acid” [22] ; by the urinary excretion of formiminoglutamic acid (FIGLU) following histidine challenge [25,26], or by the microbiological assay of serum folic acid activity [24]. But as yet, no extensive analysis has been reported of the various factors contributing to megaloblastic hemopoiesis in patients with chronic liver disease. It is the purpose of this paper to record the results of folic acid and vitamin Biz studies in nine patients with chronic liver disease and megaloblastic or transitional megaloblastic hemopoiesis, and to discuss the pathogenesis of the anemia.